We plan to investigate the effects of disturbed amino acid metabolism on brain performance, extending these studies from the molecular to the electrophysiological and behavioral levels of cerebral function. The investigations will be directed at uncovering metabolic changes in the amine, protein and lipid constituents of phenylketonuric brain, as reflected in cerebrospinal fluid, before and after phenylalanine restriction; the metabolic findings will be correlated with electrophysiological data relating to the Visual Evoked Response, which shows definitive therapeutic changes. The therapeutic strategy in Phenylketonuria will be redesigned in light of these findings.